Process for producing W/O/W type multiple emulsion for medicines

ABSTRACT

The present invention relates to a process for producing a W/O/W type multiple emulsion using a polyglycerol polyricinolate (i.e. a polyglycerol ester of a polycondensed fatty acid of caster oil). 
     The use of the polyglycerol polyricinolate is effective in increasing the rate of formation of the W/O/W type multiple emulsion remarkably and giving a W/O/W type multiple emulsion which is stable over a long period of time. The W/O/W type multiple emulsion has also an excellent heat stability and is useful for the production of medicines and cosmetics.

This application is a continuation of application Ser. No. 06/795,357,filed Oct. 15, 1985, now abandoned.

FIELD OF THE ART

The present invention relates to a process for producing a very fineW/O/W type multiple emulsion having an excellent stability.

More particularly, the present invention relates to a process forproducing a W/O/W type multiple emulsion having an excellent heatstability for the production of medicines, cosmetics, etc. other thanfood.

An object of the present invention is to produce a W/O/W type multipleemulsion useful for the production of various products in the form of anemulsion, such as medicines and cosmetics.

BACKGROUND OF THE ART

The use of W/O/W type multiple emulsions for various purposes such asthe production of cosmetics, medicines, food and drinks is expected,since generally they have a very fine texture and a smooth touch uponapplication to the skin and a water-soluble substance can beincorporated in fat globules and the apparent fat content thereof can beincreased.

In conventional processes for preparing the W/O/W type multipleemulsion, a Span (Trade Mark) emulsifier such as sorbitan monooleate isused in an amount of at least 20% based on an oil in the primaryemulsification and then the second emulsification is effected.

However, even when such a large amount of the emulsifying agent is used,the multiple-phase emulsion state is broken or the emulsification rateis reduced by heating effected in the final stage for sterilization orthe like. This is a serious demerit.

DISCLOSURE OF THE INVENTION

The inventors have now succeeded in producing an excellent W/O/W typemultiple emulsion by using a polyglycerol polyricinolate (i.e. apolyglycerol ester of a polycondensed fatty acid of castor oil) as anemulsifier.

According to the present invention, the intended effects can be obtainedwith only a small amount of the polyglycerol polyricinolate used as theemulsifier and the obtained W/O/W type multiple emulsion has anexcellent heat stability, freeze resistance and storage stability. Theinner aqueous phase is capable of containing a large amount of effectiveingredients. Since this phase is very fine, it can be formed with a highformation rate and is stable to physical treatments.

DESCRIPTION OF DRAWING

FIG. 1 shows changes in the formation rate of the W/O/W type multipleemulsion with the concentration of the emulsifiers determined in TestExample 5.

The polyglycerol polyricinolates used in the present invention arerepresented by the following formula (I): ##STR1## wherein n representsa number of 2 to 12 and R₁, R₂ and R₃ each represent a hydrogen atom ora polyricinoleic acid of the following formula (II): ##STR2## in which mrepresents a number of 2 to 10.

The polyglycerol polyricinolates of the above formula may be used eithersolely or in the form of a suitable mixture of two or more of them inthe present invention.

The polyglycerol polyricinolate (hereinafter referred to as "theemulsifier") may be incorporated in the aqueous phase, oil phase or bothof them. It is unnecessary to dissolve the former in the latter and theymay be in the form of a suspension when the emulsification is initiated.The amount of the emulsifier is about 0.1 to 20%, preferably 1 to 15%and particularly 1 to 10%, based on the oil used. If necessary, otheremulsifiers may also be used suitably. Though these emulsifiers are notparticularly limited, preferred examples of them include lecitin and/orfatty acid diesters of glycerol.

The oily substances are not limited. Examples of them include beeswax,lanolin, vaseline, paraffin, animal oils and vegetable oils. When ahardened oil is used, it should be molten by heating.

Water used in addition to the above-mentioned components may containprotein, starch, gum, emulsifier, phosphoric acid or its salt, organicacid or its salt, colorant, seasoning and medicine to form an aqueousphase and it may be kept heated.

In an embodiment of the process of the present invention for producingthe W/O/W type multiple emulsion, an aqueous phase containing anemulsifier is added gradually to an oil phase containing an emulsifierand the W/O emulsion thus obtained is inverted into a W/O/W typemultiple emulsion at once.

In another embodiment of the process of the present invention, a W/Oemulsion is prepared first by either of the following two methods. Thefirst method comprises adding an aqueous phase gradually to an oil phasecontaining an emulsifier to form a W/O emulsion directly, while thesecond method comprises adding an oil phase containing an emulsifier toan aqueous phase to form an O/W emulsion and then agitating the emulsionto invert the same into a W/O emulsion. The second method, i.e. a phaseinversion process wherein fine, uniform droplets can be formed ispreferred, though the W/O emulsion comprising fine droplets can beobtained by both methods.

In this second process, an oily substance containing the emulsifier isadded slowly to the aqueous phase under agitating.

To obtain a fine emulsion, it is not recommended to mix large amounts ofthe aqueous and non-aqueous phase at once. Though the amounts of theoily substance and water are determined suitably depending on thepurpose, a ratio of the oily substance to water of about 3:1 to 1:3 ispreferred from the viewpoint of the subsequent phase inversion.

The O/W emulsion thus obtained is agitated thoroughly with a homomixerto invert it into a W/O emulsion which is very fine and smooth. Further,medicines and various additives can be enclosed in the aqueous phasedispersed in the oil phase. The agitating with the homomixer is effectedpreferably vigorously at a rate of, for example, about 3000 to 8000 rpm.An emulsifying device such as a homogenizer or a stirring device such asa Votator may also be used. To facilitate the subsequent emulsification,the W/O emulsion is preferably heated to 50° to 80° C.

The aqueous phase is prepared as follows according to the presentinvention. The following additive(s) is(are) added to water:

casein, sodium caseinate, gelatin, wheat protein, starch, modifiedstarch, soybean protein, plasma protein, whey protein, egg white, eggyolk, dextrin, cyclodextrin, starch derivatives, locust bean gum,xanthane gum, pullulan, dextran, curdlan, guar gum, tamarind gum, agar,carrageenan, furcellaran, alginic acid and salts thereof, propyleneglycol alginate, pectin, arabinogalactan, crystalline cellulose, CMC,methylcellulose, acacia gum, tragacanth gum, Karaya gum, polysodiumacrylate, orthophosphoric acid, pyrophosphoric acid, polyphosphoric acidand salts of these phosphoric acids, common salt, vinegar, organic acidsand salts of them, emulsifiers and mixtures of these additives. Theemulsifiers used herein include sucrose fatty acid esters,polyoxyethylene sorbitan fatty acid esters, Pluronic emulsifier andTetronic emulsifier. In addition, colorants and seasonings may also beincorporated in the aqueous phase according to the purpose. It ispreferred to heat the aqueous phase to a temperature of about 50° to 80°C. to facilitate the subsequent emulsification. Though the order of theaddition is not limited, generally the W/O emulion is first placed inthe agitator and the aqueous phase containing the emulsifiers, etc. isadded thereto to perform the operation in an advantageous manner. Theagitator is not limited. The agitators usable in this process includethose having agitating blades arranged near the bottom, suction typeagitators having agitating blades extending all over the inside thereof,agitators of mere suction mixing type, homomixers, homogenizers andVotators. A preferred agitator is one in which an impact applied to theupper W/O emulsion layer is weak and a stable W/O/W type multipleemulsion can be prepared.

The aqueous phase is mixed with the above-mentioned W/O emulsion and themixture is agitated with the agitator at, for example, 250 rpm for 5min. and then treated with a homogenizer to obtain the intended W/O/Wemulsion having a very fine texture.

Thus, according to the present invention, a stable W/O/W type multipleemulsion comprising extremely fine droplets can be obtained and thisemulsion can be used in the preparation of cosmetics and medicines forexternal and internal uses.

The cosmetics which can be prepared by using said W/O/W type multipleemulsion include creams such as emolient cream, cleaning cream,foundation cream, massage cream, nutrient cream, hand cream and haircream; and lotions such as emolient lotion, cleansing lotion,aftershaving lotion, suntan lotion, hand lotion and hair treatmentlotion.

The medicines for external use include salves, poultices, medicines forburn, etc.

The medicines for internal use include internal medicines, injectionsand suppositories.

TEST 1

1%, based on the oil, of a polyglycerol polyricinolate having a degreeof polymerization of glycerol and a degree of condensation of ricinoleicacid as shown in Table 1 was added as an emulsifier to 300 g of hardenedsoybean oil at 50° C. and mixed.

The mixture was added successively to 200 g of water at 50° C. to obtainan O/W emulsion, which was agitated with a homomixer at 6000 rpm toeffect the phase inversion. Thus, a W/O emulsion was obtained.

500 g of water containing 1% of sodium caseinate and 2% of sorbitanmonostearate was heated to 70° C. The W/O emulsion heated to 70° C. wasadded thereto and the mixture was agitated in an agitator havingagitating blades arranged at the bottom thereof at 250 rpm for 5 min.The mixture was further treated in a homogenizer at 100 kg/cm² andcooled to 5° C.

The W/O/W type multiple emulsion formation rate was examined to obtainthe results shown in Table 1.

The W/O/W type multiple emulsion formation rate was determined accordingto a method of Matsumoto et al., described in "Yukagaku" 26 (10), 655(1977).

                  TABLE 1                                                         ______________________________________                                                      Degree of condensation of                                       Degree of polymeriza-                                                                       ricinoleic acid (m)                                             tion of glycerol (n)                                                                        2      3        4    5      6                                   ______________________________________                                        2             70%    72%      72%  74%    75%                                 3             75     76       76   77     78                                  4             87     93       95   95     94                                  5             85     90       94   95     94                                  6             88     89       93   95     94                                  ______________________________________                                    

The figures represent the formation rate.

Symbols n and m in Table 1 are as defined in the above formulae (I) and(II).

TEST 2 Varieties of emulsifiers for the outer aqueous phase

The same procedure as in Test 1 was repeated except that 1%, based onthe oil, of a polyglycerol polyricinolate having a degree ofpolymerization of glycerol of 4 and a degree of condensation ofricinoleic acid of 5 was used and that the emulsifier was replaced withanother emulsifier which was added in an amount of 2% based on the outeraqueous phase to obtain a W/O/W type multiple emulsion. The formationrate of the W/O/W type multiple emulsion was examined to obtain theresults shown in Table 2.

The W/O/W type multiple emulsion formation rate was determined in thesame manner as in Test 1.

                  TABLE 2                                                         ______________________________________                                        Emulsifier               Formation rate                                       ______________________________________                                        sugar ester (HLB 15.0)   95                                                   sugar ester (HLB 13.0)   95                                                   sugar ester (HLB 11.0)   95                                                   sugar ester (HLB 9.5)    94                                                   sugar ester (HLB 8.0)    91                                                   sugar ester (HLB 6.0)    87                                                   sugar ester (HLB 2.0)    82                                                   sugar ester (HLB 1.0)    75                                                   sorbitan monostearate    90                                                   sorbitan tristearate     82                                                   propylene glycol monostearate                                                                          90                                                   glycerol monostearate    83                                                   glycerol distearate      73                                                   diglycerol monostearate  87                                                   tetraglycerol monostearate                                                                             90                                                   octaglycerol monostearate                                                                              90                                                   decaglycerol monostearate                                                                              92                                                   polyoxyethylene (20) sorbitan                                                                          92                                                   monostearate                                                                  citric monoglyceride (monostearate)                                                                    88                                                   acetic monoglyceride (monostearate)                                                                    85                                                   succinic monoglyceride (monostearate)                                                                  86                                                   lactic monoglyceride (monostearate)                                                                    85                                                   diacetyltartaric monoglyceride (monostearate)                                                          87                                                   lecithin                 90                                                   ______________________________________                                    

TEST 3

The same procedure as in Test 1 was repeated using various polyglycerolpolyricinolates and emulsifiers for the outer aqueous phase. In thistest, 1%, based on the oil, of the polyglycerol polyricinolate and 2%,based on the outer aqueous phase, of the emulsifier were used and theW/O/W type multiple emulsion formation rate was determined to obtain theresults shown in Table 3.

The W/O/W type multiple emulsion formation rate was determined in thesame manner as in Test 1.

                  TABLE 3                                                         ______________________________________                                                        Formation rate (%)                                                            Polyglycerol polyricinolate                                                   Degree of  Degree                                             Emulsifier for  polymeriza-                                                                              of condensation                                    outer aqueous   tion of    of ricinoleic acid (m)                             phase           glycerol (n)                                                                             2     3   4   5   6                                ______________________________________                                        Sugar ester (HLB13.0)                                                                         2          70    73  72  74  74                                               3          76    76  77  77  77                                               4          85    92  95  95  94                                               5          86    91  94  95  95                                               6          86    91  95  94  94                               Sugar ester (HLB 8.0)                                                                         2          67    70  70  70  71                                               3          72    73  73  73  74                                               4          83    89  90  91  92                                               5          84    88  91  92  91                                               6          82    88  91  92  92                               Sugar ester (HLB 2.0)                                                                         2          62    63  63  64  65                                               3          68    69  70  70  71                                               4          80    80  82  82  81                                               5          80    81  82  82  82                                               6          81    81  81  82  81                               Sorbitan monostearate                                                                         2          70    70  72  71  72                                               3          73    73  76  75  75                                               4          82    87  90  90  90                                               5          81    87  90  90  89                                               6          81    87  89  90  89                               Glycerol monostearate                                                                         2          64    64  65  66  67                                               3          65    69  69  71  71                                               4          80    81  83  83  83                                               5          80    81  82  83  83                                               6          81    82  82  83  82                               Polyoxyethylene (20) sorbitan                                                                 2          70    73  73  73  75                               monostearate    3          73    74  76  76  76                                               4          84    89  92  92  92                                               5          85    90  92  91  92                                               6          85    89  92  92  92                               Lecithin        2          69    72  71  72  74                                               3          74    74  76  77  77                                               4          83    87  90  90  90                                               5          84    88  90  91  91                                               6          84    87  89  90  91                               ______________________________________                                    

TEST 4

The same procedure as in Test 1 was repeated except that thepolyglycerol ricinolate used in Test 1 was replaced with 1%, based onthe oil, of a mono- or polyglycerol ricinolate and that the degree ofpolymerization of glycerol and the degree of esterification ofricinoleic acid were altered. The results are shown in Table 4.

                  TABLE 4                                                         ______________________________________                                        Degree of poly-                                                                            Degree of esterification                                         merization of                                                                              of ricinoleic acid                                               glycerol     1      2          3    6                                         ______________________________________                                        1            17%    19%         0%  --%                                       2            20     18         12   --                                        3            23     28         25   --                                        6            20     28         35   43                                        10           18     27         35   42                                        ______________________________________                                    

The figures represent the formation rate.

In the following Tests 5 to 7 and examples of the present invention, thepolyglycerol polyricinolate used was a mixture of esters having a degreeof polymerization of glycerol of 3 to 4 and a degree of condensation ofricinoleic acid of 4 to 5.

TEST 5

0.5 to 10% (various), based on the oil, of a polyglycerol polyricinolateor sorbitan monooleate (Span 80) was added to 300 g of hardened soybeanoil heated to 50° C. and mixed.

The mixture was added slowly to 200 g of water heated to 50° C. toobtain an O/W emulsion, which was agitated with a homomixer at 6000 rpmto effect the phase inversion. Thus, a W/O emulsion was obtained.

500 g of water containing 1% of sodium caseinate and 2% of sorbitanmonostearate was heated to 70° C. The W/O emulsion obtained above washeated to 70° C. and added thereto and the obtained mixture was agitatedin an agitator having agitating blades arranged at the bottom thereof at250 rpm for 5 min. The mixture was further treated in a homogenizer at100 kg/cm² and cooled to 5° C.

The W/O/W type multiple emulsion formation rate was examined to obtainthe results shown in FIG. 1 wherein a curve A shows the results obtainedwhen polyglycerol polyricinolate was used and a curve B shows thoseobtained when Span 80 was used.

It is apparent from FIG. 1 that the polyglycerol polyricinolates arequite effective in the production of the W/O/W type multiple emulsion.

The W/O/W type multiple emulsion formation rate was determined accordingto a method of Matsumoto et al., described in "Yukagaku" 26 (10), 655(1977).

TEST 6

W/O/W type multiple emulsions were produced in the same manner as inTest 5 except the following points to examine the average dropletdiameter and W/O/W formation rate.

A: The same procedure as in Test 5 was repeated except that 1.0%, basedon the oil, of the polyglycerol polyricinolate was used.

B: The same procedure as in Test 5 was repeated except that 1.0%, basedon the oil, of polyglycerol polyricinolate was used and that the aqueousphase was added to the oil phase to effect the primary emulsification.

C: The polyglycerol polyricinolate used as the emulsifier was replacedwith 1.0%, based on the oil, of a mixture of sorbitan monostearate andsorbitan monooleate in a ratio of 1:1.

D: 10.0%, based on the oil, of the same mixture as in item C was used.

The results are shown in Table 5.

                  TABLE 5                                                         ______________________________________                                                   Formation rate (%)                                                            Imme-                                                                         diately                                                            Average droplet                                                                          after the                                                          diameter of W/O                                                                          prepara-   one    two   three four                                 emulsion   tion       week   weeks weeks weeks                                ______________________________________                                        A   0.6 μm  95.4       92.0 90.5  88.7  86.5                               B   1.0 μm  75.5       73.0 65.5  62.0  58.0                               C   2.5 μm  35.0       28.0 15.0  11.2  6.3                                D   1.2 μm  82.5       80.1 75.2  71.4  65.3                               ______________________________________                                         *The emulsions were stored at 5° C.                               

TEST 7

The same procedure as in Test 5 was repeated except that thepolyglycerol polyricinolate was replaced with 1%, based on the oil, ofanother emulsifier to obtain a W/O/W emulsion. The average dropletdiameter and W/O/W type multiple emulsion formation rate were examined.Further, the W/O/W type multiple emulsion formation rates after storageat 5° C. for one month and after heating at 120° C. for 30 min were alsoexamined to obtain the results shown in Table 6.

The W/O/W type multiple emulsion formation rate was determined in thesame manner as in Test 5.

                  TABLE 6                                                         ______________________________________                                                                 Formation Formation                                                           rate after                                                                              rate after                                          Average                                                                              Forma-   storage at                                                                              heating at                                          droplet                                                                              tion     5° C. for 1                                                                      120° C. for                                  diameter                                                                             rate (%) month (%) 30 min (%)                                 ______________________________________                                        1   polyglycerol                                                                             0.6      95.4   86.5    95                                         polyricinolate                                                            2   lecithin   2.7      30.2   5.0     19                                     3   glycerol   3.8      18.5   2.7     15                                         monostearate                                                              4   glycerol   2.2      28.3   4.3     32                                         monooleate                                                                5   diglycerol 4.3      14.1   3.0     10                                         monostearate                                                              6   diglycerol 1.8      40.2   12.0    35                                         monooleate                                                                7   sorbitan   3.3      17.3   3.5     11                                         tristearate                                                               8   sucrose fatty                                                                            4.1      11.0   4.6      7                                         acid ester                                                                ______________________________________                                        Example 1 Cleansing cream                                                     ______________________________________                                        1.      beeswax             10     wt. %                                      2.      lanolin             3      wt. %                                      3.      vaseline            10     wt. %                                      4.      liquid paraffin     42     wt. %                                      5.      polyglycerol polyricinolate                                                                       4      wt. %                                      6.      perfume             0.5    wt. %                                      7.      purified water      30.5   wt. %                                                                  100.0  wt. %                                      ______________________________________                                    

The above components 1 to 4 were heated to 50° C. The component 5 wasadded to the mixture and mixed.

Separately, the component 7 was heated to 50° C. and the component 6 wasadded thereto. The above-mentioned oily mixture was added thereto at arate of 20 ml/min under agitating at 6000 rpm. In the course of thisstep, the O/W emulsion was inverted to obtain a W/O emulsion. 100 partsby weight of the W/O emulsion was dispersed in 20 parts by weight of a10% aqueous solution of polyoxyethylene sorbitan monolaurate. Thedispersion was emulsified again with a homomixer at 80° C. to obtain acleansing cream comprising essentially the W/O/W type multiple emulsion.

The obtained cleansing cream was free of a greasy touch and realized afresh feeling upon use. The cream had very excellent spreadability andcleansing effects and a stable emulsion state.

    ______________________________________                                        Example 2 Massage cream                                                       ______________________________________                                        1.      anhydrous lanolin   10     wt. %                                      2.      vaseline            50     wt. %                                      3.      hardened fat        1      wt. %                                      4.      liquid paraffin     10     wt. %                                      5.      perfume             0.5    wt. %                                      6.      polyglycerol polyricinolate                                                                       5      wt. %                                      7.      purified water      23.5   wt. %                                                                  100.0  wt. %                                      ______________________________________                                    

The above components 1 to 4 were heated to 50° C. The component 6 wasadded to the mixture and the component 5 was added thereto underagitating with a homomixer at 6000 rpm. The component 7 heated to 50° C.was added successively to the mixture to obtain a W/O emulsion.

100 parts by weight of the W/O emulsion was dispersed in 20 parts byweight of a 10% aqueous solution of polyoxyethylene sorbitan monoleate.The dispersion was emulsified again with a homomixer at 80° C. to obtaina massage cream comprising essentially the W/O/W type multiple emulsion.

    ______________________________________                                        Example 3 Hand cream                                                          ______________________________________                                        1.     beeswax          10        wt. %                                       2.     vaseline         12        wt. %                                       3.     liquid paraffin  35        wt. %                                       4.     solid paraffin   10        wt. %                                       5.     polyglycerol polyricinolate                                                                    3         wt. %                                       6.     purified water   30        wt. %                                                               100.0     wt. %                                       ______________________________________                                    

The above components 1 to 5 were heated to 50° C. The component 6 heatedto 50° C. was added successively to the mixture under agitating with ahomomixer at 6000 rpm to obtain a W/O emulsion.

100 parts by weight of this emulsion was dispersed in 25 parts by weightof a 10% aqueous solution of polyoxyethylene sorbitan monooleate. Thedispersion was emulsified again with a homomixer at 80° C. to obtain ahand cream comprising essentially the W/O/W type multiple emulsion.

    ______________________________________                                        Example 4 Hair cream and hair lotion                                          ______________________________________                                        1.    beeswax           2         wt. %                                       2.    liquid paraffin  45.5       wt. %                                       3.    polyglycerol polyricinolate                                                                    2.5        wt. %                                       4.    purified water   50         wt. %                                       5.    perfume          a small amount                                                           100.0   wt. %                                               ______________________________________                                    

The above components 1 and 3 were heated to 50° C. The component 5 wasadded thereto under stirring with a homomixer at 6000 rpm and then thecomponent 4 heated to 50° C. was added slowly to the mixture to obtain aW/O emulsion.

(1) Hair cream

100 parts by weight of the W/O emulsion was dispersed in 20 parts byweight of a 10% aqueous solution of polyoxyethylene sorbitanmonolaurate. The dispersion was emulsified again with a homomixer at 80°C. to obtain a hair cream comprising essentially the W/O/W type multipleemulsion.

(2) Hair lotion

100 parts by weight of the W/O emulsion obtained as above was dispersedin 100 parts by weight of purified water containing 2% of a sorbitanmonopalmitate and 2% of a polyoxyethylene monostearate. The dispersionwas emulsified again with a homomixer at 80° C. to obtain a hair lotioncomprising essentially the W/O/W type multiple emulsion.

    ______________________________________                                        Example 5 Cleansing lotion                                                    ______________________________________                                        1.     beeswax          3.0 wt. %                                             2.     solid paraffin   5.0 wt. %                                             3.     vaseline         10.0 wt. %                                            4.     liquid paraffin  30.0 wt. %                                            5.     polyglycerol polyricinolate                                                                    6.0 wt. %                                             6.     perfume          0.5 wt. %                                             7.     purified water   45.5 wt. %                                                                    100.0 wt. %                                           ______________________________________                                    

The above components 1 to 5 were heated to 50° C. The component 6 wasadded to the mixture under agitating with a homomixer at 6000 rpm andthen the component 7 heated to 50° C. was added slowly to the mixture toobtain a W/O emulsion.

100 parts by weight of the obtained emulsion. was dispersed in 40 partsby weight of a 5% aqueous solution of polyoxyethylene sorbitanmonooleate. The dispersion was emulsified again with T. K. Homo Mixer at80° C. to obtain a cleansing lotion comprising essentially the W/O/Wtype multiple emulsion.

EXAMPLE 6

12,000 units of insulin was dissolved in 8 ml of 0.1N hydrochloric acidto obtain an aqueous insulin solution.

Separately, 1.5 g of a polyglycerol polyricinolate was dissolved in 30ml of salad oil. The aqueous solution containing insulin was addeddropwise to the latter solution over 3 min in an ultrasonic generator toobtain a W/O emulsion.

This emulsion was added dropwise to 100 ml of a 2% aqueouspolyoxyethylene fatty acid ester solution and the mixture was emulsifiedagain with the same ultrasonic generator for 5 min to obtain 136 ml ofan insulin-containing W/O/W type multiple emulsion.

EXAMPLE 7

140,000 units of insulin was dissolved in 120 ml of 0.1N hydrochloricacid solution to obtain an aqueous solution containing insulin.

Separately, 10 g of a polyglycerol polyricinolate was dissolved in 200ml of soybean oil. The aqueous solution containing insulin was addeddropwise to the latter solution and the mixture was emulsified in ahigh-pressure emulsifying device for 10 min to obtain a W/O emulsion.

This emulsion was added dropwise to 900 ml of a 1% aqueous solution of apolyoxyethylene monostearate ester and the mixture was emulsified againin the same device for 15 min to obtain 1340 ml of a W/O/W type multipleemulsion.

EXAMPLE 8

    ______________________________________                                        1.     Inner aqueous phase:                                                          maltose              0.19   g                                                 triethanolamine      0.03   g                                                 distilled water      18     g                                          2.     oil phase:                                                                    polyglycerol polyricinolate                                                                        2      g                                                 soybean lecithin     0.07   g                                                 olive oil            2.5    g                                                 stearic acid         0.63   g                                                 predonisolone (0.1 wt. %)                                                                          0.05   g                                          3.     outer aqueous phase:                                                          Pluronic F-68        0.12   g                                                 sucrose monolaurate  0.06   g                                                 triethanolamine      0.06   g                                                 distilled water      22.4   g                                          ______________________________________                                    

The mixture 1 was added slowly to the mixture under agitating with ahomomixer at 6000 rpm to obtain a W/O emulsion.

The obtained emulsion was dispersed in the mixture 3 and emulsifiedagain with the homomixer to obtain a salve comprising essentially theW/O/W type multiple emulsion.

What is claimed is:
 1. A process for producing a W/O/W type multipleemulsion for the production of medicines and cosmetics, comprising thesteps of:(a) adding an emulsifying amount of polyglycerolpolyrincinoleate to an oil phase; (b) forming a W/O emulsion by addingan aqueous phase to the product obtained in step (a); (c) forming theW/O/W emulsion by adding said W/O emulsion obtained by step (b) to anouter aqueous phase; (d) including a medicine or cosmetic within theW/O/W emulsion.
 2. A process for producing a W/O/W type multipleemulsion for the production of medicines and cosmetics, comprising thesteps of:(a) adding an emulsifying amount of polyglycerolpolyricinoleate to an aqueous phase; (b) forming a W/O emulsion byadding the product obtained by step (a) to an oil phase; (c) forming theW/O/W emulsion by adding said W/O emulsion obtained by step (b) to anouter aqueous phase.
 3. A process for producing a W/O/W type multipleemulsion for the production of medicines and cosmetics, comprising thesteps of:(a) forming a W/O emulsion by adding an aqueous phase to an oilphase; (b) adding an emulsifying amount of polyglycerol polyricinoleateto an outer aqueous phase; (c) forming the W/O/W emulsion by adding saidW/O emulsion obtained by step (a) to the product obtained by step (b).